Bcl-2 family
Bcl-2 family
regulators of apoptosis
regulators of apoptosis
Jakub Kubiak
Jakub Kubiak
Bcl-2 family
Bcl-2 family
regulators of apoptosis
regulators of apoptosis
Jakub Kubiak
Jakub Kubiak
Short history of Bcl-2
Short history of Bcl-2
Discoverd in B-cell
Discoverd in B-cell
lymphoma
lymphoma
T(14:18)
T(14:18)
translocation
translocation
BCL-2
BCL-2
gene pleaced
gene pleaced
next to the Ig heavy
next to the Ig heavy
chain locus
chain locus
Proto-oncogene
Proto-oncogene
Play a role in
Play a role in
apoptosis
apoptosis
Apoptosis – what’s that?
Apoptosis – what’s that?
From Greek – falling of
From Greek – falling of
Name suggested by prof Cormack
Name suggested by prof Cormack
First featured by Kerr, Wylie and Currie
First featured by Kerr, Wylie and Currie
Cell death progamm
Cell death progamm
Apoptosis – what does it
Apoptosis – what does it
for?
for?
Features of apoptosis
Features of apoptosis
Blebbig cell surface
Blebbig cell surface
Organelle
Organelle
compaction
compaction
Chromatin
Chromatin
condensatation
condensatation
and cleavage by
and cleavage by
endonuclease
endonuclease
Cell fragmentation
Cell fragmentation
Phagocytosis
Phagocytosis
Failure of apoptosis may
Failure of apoptosis may
lead disease
lead disease
Cancer
Cancer
Neurodegenration
Neurodegenration
Autoimmune disease
Autoimmune disease
Persistant infections
Persistant infections
Ischaemia
Ischaemia
AIDS
AIDS
Bcl-2 family
Bcl-2 family
3 main groups
3 main groups
Similar
Similar
domains: BH1,
domains: BH1,
BH2, BH3
BH2, BH3
Opposite
Opposite
activity: pro-
activity: pro-
and anti-
and anti-
apoptotic
apoptotic
Structure of Bcl-x
Structure of Bcl-x
L
L
7 alfa–helices
7 alfa–helices
3 domains BH1, BH2
3 domains BH1, BH2
and BH3
and BH3
BH1 & BH2 death
BH1 & BH2 death
receptor domain
receptor domain
(mutations in these
(mutations in these
domains abolish anti-
domains abolish anti-
apoptotic activity)
apoptotic activity)
BH3 death domain
BH3 death domain
Transmembrane
Transmembrane
domain
domain
Mechanism of regulation -
Mechanism of regulation -
simply
simply
Bcl-2 regulates
Bcl-2 regulates
activation of
activation of
caspases
caspases
Bcl-2 and BAX
Bcl-2 and BAX
dimerise and
dimerise and
loose their activity
loose their activity
Apoptosis depend
Apoptosis depend
on level of pro-
on level of pro-
and antiapoptotic
and antiapoptotic
members of Bcl-2
members of Bcl-2
family
family
Regulation – less simply
Regulation – less simply
Very
Very
complicated
complicated
Real very
Real very
coplicated
coplicated
Mechanism of
Mechanism of
regulation
regulation
unknown, only
unknown, only
hypothesis
hypothesis
Cancer caused by Bcl-2
Cancer caused by Bcl-2
Bcl-2 caused cancer by impair apoptosis
Bcl-2 caused cancer by impair apoptosis
Bcl-2 is overexpressed
Bcl-2 is overexpressed
Cancer cells don’t go under apoptosis
Cancer cells don’t go under apoptosis
Cancer cells are less vulnerable to
Cancer cells are less vulnerable to
chemotherapy and radiotherapy
chemotherapy and radiotherapy
Treatment
Treatment
Bcl-2 antisense therapy (decreas the
Bcl-2 antisense therapy (decreas the
number of Bcl-2)
number of Bcl-2)
Bcl-2 family proteins are
Bcl-2 family proteins are
intensively examined
intensively examined
Reserches on many kinds of cancer
Reserches on many kinds of cancer
Reserches on apoptosis
Reserches on apoptosis
But still many informations remain
But still many informations remain
unknown
unknown
Some interesting links about
Some interesting links about
apoptosis and Bcl-2 family
apoptosis and Bcl-2 family
http://users.rcn.com/jkimball.ma
http://users.rcn.com/jkimball.ma
.ultranet/BiologyPages/A/Apoptos
.ultranet/BiologyPages/A/Apoptos
http://www.portfolio.mvm.ed.ac.u
http://www.portfolio.mvm.ed.ac.u
k/studentwebs/session2/group28/b
k/studentwebs/session2/group28/b
http://www.celldeath.de/encyclo/
http://www.celldeath.de/encyclo/
Thank you
Thank you